Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
J Clin Invest. 2013 Jul;123(7):2965-8. doi: 10.1172/JCI67201. Epub 2013 Jun 17.
Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.
腺样囊性癌（ACC）是一种罕见的恶性肿瘤，可发生在多个器官部位，主要发生在唾液腺。虽然已经开始确定 MYB-NFIB 基因的反复融合，以揭示其分子基础，但对于这种经常致命的癌症的分子遗传学知之甚少。我们对一系列 24 例 ACC 进行了外显子组测序，以进一步阐明该疾病的遗传学。我们鉴定了多个突变基因，这些基因的突变联合表明一半的病例存在染色质失调。此外，还鉴定出了已知的癌症基因中的突变，包括 PIK3CA、ATM、CDKN2A、SF3B1、SUFU、TSC1 和 CYLD。3 例中存在 NOTCH1/2 突变，我们鉴定出 Notch 信号负调节因子 SPEN 是 ACC 的一个新的癌症基因，在 5 例中存在突变。最后，鉴定出 3 例 FGFR2 酪氨酸激酶受体的可能激活突变，类似于卵巢癌和子宫内膜癌中报道的突变，这为一部分病例提供了潜在的治疗途径。
